While cocaine abuse and addiction are serious problems facing our society today, there is currently no widely accepted pharmacological treatment for cocaine dependence. In clinical trials using the drug disulfiram, significant efficacy in preventing cocaine administration has been observed. However, the mechanism by which disulfiram attenuates cocaine use is unknown. Based on the literature, as well as preliminary results from our laboratory, inhibition of the enzyme Dopamine Beta-hydroxylase (DBH) appears to be a good candidate for the target which mediates disulfiram's clinical effect. DBH is the enzyme that converts dopamine to norepinephrine in the catecholamine synthetic pathway. The use of drugs that inhibit DBH, as well as mice that have genetic knockout of the Dbh gene, will enable us to explore the involvement of this enzyme in disulfiram's effects. Disulfiram's influence on multiple drug-induced behaviors will be examined including cocaine induced place preference, aversion, drug seeking, and anxiety. Understanding the mechanism of action by which disulfiram attenuates cocaine use will increase our knowledge about drug addiction in general, as well as help identify targets for future exploration in medication development. [unreadable] [unreadable] [unreadable]